Francisella tularensis is the causative agent for the potentially fatal disease tularemia. The lipoprotein Flpp3 has been identified as a virulence determinant of tularemia with no sequence homology outside the Francisella genus. We report a room temperature structure of Flpp3 determined by serial femtosecond crystallography that exists in a significantly different conformation than previously described by the NMR-determined structure. Furthermore, we investigated the conformational space and energy barriers between these two structures by molecular dynamics umbrella sampling and identified three low-energy intermediate states, transitions between which readily occur at room temperature. We have also begun to investigate organic compounds in silico that may act as inhibitors to Flpp3. This work paves the road to developing targeted therapeutics against tularemia and aides in our understanding of the disease mechanisms of tularemia.

中文翻译：

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弗朗西斯菌脂蛋白的 XFEL 和 NMR 结构揭示了针对土拉菌病的药物靶点的构象空间。

土拉弗朗西斯菌是潜在致命疾病土拉菌病的病原体。脂蛋白 Flpp3 已被确定为土拉菌病的毒力决定因素，在弗朗西斯菌属之外没有序列同源性。我们报告了由连续飞秒晶体学确定的 Flpp3 的室温结构，该结构与以前由 NMR 确定的结构描述的构象存在显着不同的构象。此外，我们通过分子动力学伞形采样研究了这两种结构之间的构象空间和能垒，并确定了三种低能中间态，它们之间的转变很容易在室温下发生。我们还开始研究可作为 Flpp3 抑制剂的计算机有机化合物。